The human immunodeficiency virus (HIV) and various mutants including type 1 (HIV-1), is the etiological agent of acquired immune deficiency syndrome (AIDS) and related disorders. DNA synthesis during reverse transcriptase is a crucial step in the virus life cycle of human immunodeficiency virus (HIV), and therefore compounds that affect DNA synthesis during the reverse transcriptase process are candidates for antiretroviral therapy. The screening and investigation of novel drugs against HIV remains critical because of the ongoing AIDS epidemics and of the fast emergence of virus variants resistant to present antiviral therapy. The replication steps of HIV, a member of the retrovirus family, are well known and can therefore be targeted rationally.
Substituted-2-deoxyadenosine compounds which are substituted at the C4′-position with variously substituted groups are known, and some have been disclosed as useful in treating viral infection, including HIV. Various 2-Deoxyadenosine compounds have been disclosed having a methyl, ethynyl, halomethyl, halovinyl, or nitrile substitution at the C4′ position. These compounds have been shown to be useful against HIV but have been limited to due problematic cytotoxicity ranges.
The instant invention seeks to provide novel substituted-2-deoxyadenosine compounds that are useful to treat HIV, wherein such compounds have reduced cytotoxicity profiles.